AKT2 Blocks Nucleus Translocation of Apoptosis-Inducing Factor (AIF) and Endonuclease G (EndoG) While Promoting Caspase Activation during Cardiac Ischemia

Yang, Shuai; Zhao, Xinmei; Xu, Hui; Chen, Fan; Xu, Yitao; Li, Zhe; Sanchis, Daniel; Jin, Liang; Zhang, Yubin; Ye, Junmei

doi:https://doi.org/10.3390/ijms18030565

View/Open

025734 .pdf (5.080Mb)

Issue date

2017

Author

Yang, Shuai

Zhao, Xinmei

Xu, Hui

Chen, Fan

Xu, Yitao

Li, Zhe

Sanchis, Daniel

Jin, Liang

Zhang, Yubin

Ye, Junmei

Suggested citation

Yang, Shuai; Zhao, Xinmei; Xu, Hui; Chen, Fan; Xu, Yitao; Li, Zhe; ... Ye, Junmei. (2017) . AKT2 Blocks Nucleus Translocation of Apoptosis-Inducing Factor (AIF) and Endonuclease G (EndoG) While Promoting Caspase Activation during Cardiac Ischemia. International Journal of Molecular Sciences, 2017, vol. 18, núm. 565, p. 1-18. https://doi.org/10.3390/ijms18030565.

Abstract

The AKT (protein kinase B, PKB) family has been shown to participate in diverse cellular processes, including apoptosis. Previous studies demonstrated that protein kinase B2 (AKT2 − / − ) mice heart was sensitized to apoptosis in response to ischemic injury. However, little is known about the mechanism and apoptotic signaling pathway. Here, we show that AKT2 inhibition does not affect the development of cardiomyocytes but increases cell death during cardiomyocyte ischemia. Caspase-dependent apoptosis of both the extrinsic and intrinsic pathway was inactivated in cardiomyocytes with AKT2 inhibition during ischemia, while significant mitochondrial disruption was observed as well as intracytosolic translocation of cytochrome C (Cyto C) together with apoptosis-inducing factor (AIF) and endonuclease G (EndoG), both of which are proven to conduct DNA degradation in a range of cell death stimuli. Therefore, mitochondria-dependent cell death was investigated and the results suggested that AIF and EndoG nucleus translocation causes cardiomyocyte DNA degradation during ischemia when AKT2 is blocked. These data are the first to show a previous unrecognized function and mechanism of AKT2 in regulating cardiomyocyte survival during ischemia by inducing a unique mitochondrial-dependent DNA degradation pathway when it is inhibited.

URI

http://hdl.handle.net/10459.1/60024

DOI

https://doi.org/10.3390/ijms18030565

Is part of

International Journal of Molecular Sciences, 2017, vol. 18, núm. 565, p. 1-18

Collections

The following license files are associated with this item:

Creative Commons

Except where otherwise noted, this item's license is described as cc-by (c) Yang., 2017